Localization of uridine 5′-diphosphate-glucuronosyltransferase in human liver injury

Henry S. Debinski, C. Soon Lee, Janine A. Danks, Peter I. Mackenzie, Paul V. Desmond

    Research output: Contribution to journalArticle

    34 Citations (Scopus)

    Abstract

    Background/Aims Pharmacokinetic studies in patients with cirrhosis have shown a decreased clearance of drugs metabolized by cytochrome P450, whereas drugs metabolized by glucuronidation frequently have a normal elimination. The mechanism for the apparent preservation of glucuronidation has not been elucidated. The aim of this study was to examine the expression of uridine 5′-diphosphate-glucuronosyltransferase (UGT) in human liver injuries. Methods UGT was measured by immunohistochemistry using a UGT polyclonal antibody, which was then compared with a representative isoform of cytochrome P450. Normal liver biopsy specimens (n = 8) and a spectrum of liver injury biopsy specimens (n = 47) were examined. Results Compared with normal liver, increased staining for UGT in remaining hepatocytes was seen in liver damaged by chronic alcohol abuse, but the most intense immunoreactivity was observed in remaining and regenerative hepatocytes in specimens with cirrhosis. Primary biliary cirrhosis showed diffusely increased immunoreactivity. Other nonmalignant groups showed an increased staining relative to chronicity of liver disease. In contrast, in all liver injuries, cytochrome P450 staining was reduced as compared with controls. Conclusions Chronic liver damage results in increased UGT in remaining viable hepatocytes. Mechanisms may operate in liver injury to preserve expression of UGT in functional hepatocytes, and this may explain the preservation of glucuronidation in cirrhosis.

    Original languageEnglish
    Pages (from-to)1464-1469
    Number of pages6
    JournalGastroenterology
    Volume108
    Issue number5
    DOIs
    Publication statusPublished - May 1995

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